DESCRIPTION (Taken from application) Oral tolerance is the phenomenon of specific systemic tolerance established after ingestion of an antigen. Mounting evidence indicates that oral tolerance regimens may be a useful approach in the treatment of immunemediated diseases. Oral tolerance may therefore be considered as a possible novel mode of therapy for ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease (IBD). However, since intestinal immunity is abnormal in IBD, it is unclear if oral tolerance would be an effective therapeutic strategy for these diseases. As the basis for future therapeutic trials of oral tolerance in IBD, the hypothesis that oral tolerance is aberrant in IBD will be tested. This will be accomplished by comparing healthy subjects and patients with Crohn's disease or ulcerative colitis with regard to their ability to achieve specific systemic T cell tolerance after a regimen of antigen ingestion. The effect of prior feeding upon the subsequent development of specific systemic T cell tolerance, as measured by antigen-specific T cell proliferation and skin delayed hypersensitivity will be compared. The effects of disease characteristics, as well as nutritional state, age, gender, smoking history, and history of prior appendectomy on the development of oral tolerance will also be explored in order to define appropriate inclusion criteria for future clinical trials. As an alternative approach, a regimen of nasal inhalation will investigated as a means of achieving systemic tolerance. This will permit testing of the hypothesis that aberrant oral tolerance in IBD is a consequence of altered intestinal mucosal function, and could provide an alternate route of administration for use in therapeutic protocols. Finally, appropriate candidate antigens and laboratory endpoints for tolerance regimens will be identified. The data obtained in these investigations should provide sufficient background to permit the design of a therapeutic trial of mucosal tolerance, whether by oral or nasal route, in IBD.